Note: Javascript is disabled or is not supported by your browser. For this reason, some items on this page will be unavailable. For more information about this message, please visit this page: About CDC.gov.

Warning:

This online archive of the CDC Prevention Guidelines Database
is being maintained for historical purposes, and has had no new entries
since October 1998. To find more recent guidelines, please visit the following:

Publication date: 11/14/1997

Table of Contents

Article

In 1997, a nongovernmental surveillance group for
Creutzfeldt-Jakob disease (CJD) in Japan reported to the Ministry
of Health and Welfare its analysis of a 1996 mail questionnaire
survey of neurologic, psychiatric, and neuropathologic institutions
throughout Japan. This analysis identified 829 patients with CJD
diagnosed by physicians during January 1979-May 1996, including a
large number (43 patients) who had received a cadaveric dura mater
graft during a neurosurgical (42) or orthopedic (one) procedure
during 1979-1991. This report presents a summary of features of
these 43 cases, which indicated that at least 41 of these patients
had received dura mater grafts from the same processor, and
describes CJD in the most recent recipient of a dura mater graft.
The findings indicate that an international outbreak of CJD
associated with a single brand of dura mater grafts is larger than
previously recognized and that recipients of contaminated grafts
may remain at risk for CJD at least 16 years following receipt of
grafts.

Summary Findings

Of the 4017 institutions surveyed, 2962 (74%) responded.
Follow-up investigation of the 43 CJD cases associated with dura
mater grafts revealed that at least 41 (95%) persons had received
a single brand of dura mater graft, LYODURA{Registered} *, processed
by B. Braun Melsungen AG. The grafts had been processed before May
1987, when the company revised its procedures for collection and
processing dura. The revised procedures, designed to reduce the
risk for CJD transmission, included conversion from batch to
individual processing of dura mater and treatment of each dura
mater graft with 1.0 normal sodium hydroxide (NaOH).

The 43 patients with CJD had onsets of illness from September
1985 to May 1996 (Figure 1). The mean (plus or minus 1 standard
deviation) age of the 43 patients at onset of dura mater
graft-associated CJD was 53 years (plus or minus 13 years) compared
with a mean age at onset (63 years {plus or minus 10 years}) of the
other CJD cases identified in this survey (pless than 0.05); of the
43 patients who had received a dura mater graft, eight were aged
less than 40 years at onset of CJD. The mean latency period between
receipt of a dura mater graft and onset of CJD was 89 months (plus
or minus 44 months) (range: 16-193 months). Neuropathologic
examinations were performed for 10 decedents who underwent autopsy;
typical spongiform degeneration was present in the cerebral and
cerebellar cortex of all 10.

Of the 43 CJD patients, 42 received their dura mater graft
during 1979-1989 (Figure 2). All but one of the 42 patients were
reported to have received LYODURA{Registered} that had been
processed without exposure to NaOH. The brand of graft used in one
patient who had undergone a neurosurgical operation in 1985 was
unknown; however, LYODURA{Registered} was the only brand of dura
mater graft used at the hospital. A total of 33 (77%) of the
patients received their grafts during 1983-1987 (Figure 2), when an
estimated 100,000 patients may have received LYODURA{Registered} in
Japan. All of these 33 patients died of CJD within 12 years after
receipt of the grafts (approximately 1 case of CJD per 3000
LYODURA{Registered} recipients). None of the lot numbers of the
dura mater grafts used in the 43 patients could be identified.
Case Description

The most recent recipient of a dura mater graft among the 43
graft-associated CJD patients was a woman aged 65 years at the time
of onset of CJD. She had two neurosurgical procedures in 1991 to
repair a cerebral arterial aneurysm (one in September and one in
October); dura mater grafts were used during both operations. In
February 1994, 28 months after the second operation, she developed
progressive dysphagia, dysarthria, and unsteady gait, followed
within a few weeks by dementia. In April 1995, she developed
generalized myoclonic jerks and akinetic mutism. An
electroencephalograph showed a 6- to 10-Hz background rhythm with
the periodic synchronized slow activity complexes typical of CJD.
Examination of the cerebrospinal fluid revealed a normal protein
level and cell count. A magnetic resonance imaging scan showed
marked cerebral and cerebellar atrophy. The patient died in October
1995, and no autopsy was performed.

Neither the brand nor year of processing of the dura mater
grafts used in this patient in 1991 could be determined. However,
the hospital in which both neurosurgical procedures were performed
opened in 1989 and reported using only two brands of dura mater
grafts in 1991, LYODURA{Registered} and Tutoplast (Pfrimmer-Viggo
GmbH+Co, Erlangen, Germany). The investigation suggested that in
this patient, the use of LYODURA{Registered} processed before May
1987 was unlikely but could not be ruled out.

Editorial Note

Editorial Note: In June 1987, after an investigation of the first
reported LYODURA{Registered}-associated CJD case (1), CDC published
a description of differences between the processing of
LYODURA{Registered} and other similar products and suggested that
LYODURA{Registered} may be associated with a higher risk for
transmitting CJD than other dura mater products used in the United
States (2). Also in June 1987, representatives of B. Braun
Melsungen AG reported that as of May 1, 1987, their procedures for
collecting and processing dura were revised to reduce the risk for
CJD transmission (3). By including the present report from Japan,
the total number of reported LYODURA{Registered}-associated CJD
cases has now increased to at least 61 worldwide (3-5).

Despite limitations in the information about the number and
subsequent vital status of recipients of LYODURA{Registered} and
other dura mater grafts, the findings and evidence in this report
strongly indicate that the LYODURA{Registered} grafts were the
vehicle of transmission of the CJD agent in Japan. This evidence
includes the high overall estimated incidence of CJD among the
LYODURA{Registered} graft recipients and the identification, almost
exclusively, of the same brand of graft produced during the same
early period that had been associated with at least 21 other
reported CJD cases worldwide.

In comparison with the strong evidence of CJD transmission by
LYODURA{Registered} produced before May 1987, the evidence in Japan
is substantially weaker for CJD transmission by a
non-LYODURA{Registered} brand of graft or a LYODURA{Registered}
graft produced after May 1987; such an association was reported as
likely in only one CJD patient who was not unusually young.
However, for this patient, the investigation cannot exclude a
causal relation between disease and receipt of a graft other than
LYODURA{Registered} produced before May 1987. Even stringent donor
screening and processing of each dura separately to avoid possible
cross-contamination may not completely eliminate the potential for
an infectious graft. In addition, the treatment of dura with NaOH
may not inactivate all of the infectious agent that may be present
(6). Therefore, surgeons should be aware of the possibly inherent
risk for CJD transmission by dura mater grafts and may want to
consider the alternative use of autologous fascia lata, fascia
temporalis, or synthetic substitutes (4).

The cases described in this report indicate that recipients of
contaminated grafts may remain at risk for CJD at least 16 years
after receiving grafts. In the United States, patients who have
rapidly progressive dementing illnesses consistent with CJD and who
have received an allograft should be reported through their
respective local or state health departments to CDC's Division of
Viral and Rickettsial Diseases, National Center for Infectious
Diseases, telephone (404) 639-3091.

References

References

CDC. Rapidly progressive dementia in a patient who received a
cadaveric dura mater graft. MMWR 1987;36:49-50,55.

* Use of trade names and commercial sources is for identification
only and does not imply endorsement by CDC or the U.S. Department
of Health and Human Services.

POINT OF CONTACT FOR THIS DOCUMENT:

To request a copy of this document or for questions concerning this
document, please contact the person or office listed below. If
requesting a document, please specify the complete name of the
document as well as the address to which you would like it mailed.
Note that if a name is listed with the address below, you may wish
to contact this person via CDC WONDER/PC e-mail.